Chimeric antigen receptor (CAR)-T cell therapies have gone down in history as a major breakthrough in cancer treatment. Although more advanced cell therapies attempt to overcome the limitations of CAR-T, it has been a significant advancement in cancer research, and more and more companies are joining the pursuit of new innovative approaches in the field.
CAR-T typically works by collecting a patient’s T cells and engineering them to recognise and target a specific protein on cancer cells. Once these engineered cells are grown in the lab, they are sent back into the patient’s bloodstream, where the cells then go on to attack cancer cells.
In this article, we take a look at eight promising biotech companies that are advancing their CAR-T cell therapy candidates in the clinic.
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Allogene Therapeutics
Allogene Therapeutics aims to tackle the limitations of autologous CAR-T therapies by developing allogeneic CAR-T cell therapy products. Allogeneic therapies use T cells from healthy donors.
Once retrieved, the cells are isolated and engineered to express CARs. These CARs are then able to recognize and attack cancer cells. Moreover, they are modified with the help of gene editing to mitigate side effects. The American CAR-T company has a number of candidates in its roster. The most advanced is cema-cel, anti-CD19 CAR T therapy, which is in a phase 2 trial to treat patients with large B-cell lymphoma (LBCL)
It is also testing cema-cel in a phase 1 trial targeting the CD19 antigen in patients with relapsed/refractory chronic lymphocytic leukemia. Moreover, it is targeting the B-cell maturation antigen (BCMA) in two phase 1 trials studying its CAR-T candidates, ALLO-715 and ALLO-6053 for multiple myeloma.
Only recently, Allogene announced that it had halted two B-cell lymphoma phase 2 trials of cema-cel in order to reshift focus and begin a trial with patients who have minimal residual disease (MRD), citing that its CAR-T therapy would make later-line treatment obsolete.
Anixa Biosciences
Focused on cancer care, Anixa Biosciences is a company specializing in the field of CAR-T cell therapy and cancer vaccines. It is targeting the CD19 protein because it is only present in B cells, making the biotech’s approach more target-specific. Anixa aims to kill cancerous B cells while leaving healthy B cells untouched.
Having collaborated with Moffitt Cancer Center, it is conducting a phase 1 study in patients with ovarian cancer. This candidate is a new type of CAR-T called a chimeric endocrine receptor T-cell therapy or a CER T therapy. The autologous therapy targets the follicle stimulating hormone receptor (FSHR), which is present on the ovaries.
Last month, the U.S.-based biotech dosed its first patient in the second cohort of its trial that is evaluating a dose three times higher than the one given to patients in the first cohort. It also has a CAR-T therapy being assessed in preclinical trials for solid tumors.
Autolus Therapeutics
A frontrunner in CAR-T therapies, British company Autolus Therapeutics aims to bring its range of cell therapies to the market soon.
Most advanced in the pipeline is obe-cel. Targeting CD19, the candidate is designed to bind-off quickly to minimize excessive activation of the programmed T cells. Earlier this year, its Biologics License Application was cleared by the U.S. Food and Drug Administration (FDA) for relapsed/refractory adult B-cell acute lymphoblastic leukemia, for which it has completed a pivotal trial, and is awaiting the FDA’s response. The pivotal study met its primary endpoint at an interim analysis and a 70% overall response rate was observed.
Obe-cel is also in two other phase 1 trials to treat patients with large B cell lymphoma, chronic lymphocytic leukemia and primary central nervous system (CNS) lymphoma.
In February, it bagged $350 million in a public offering from BioNTech, having secured a total of $600 million including $250 million from its partnership with BioNTech. Through this deal, BioNTech gains exclusive license to Autolus’ target binders, and in turn, it will support the potential launch of Autolus’ obe-cel.
BioNTech
German biotech company BioNTech is known for bringing its mRNA cancer vaccines to the clinic, but its CAR-T candidate is no less competent.
BNT211 comprises two drug products: autologous CAR-T cell therapy targeting the oncofetal antigen Claudin-6 and a CLDN6-encoding CAR-T cell amplifying RNA vaccine, CARVac, which is based on its mRNA-lipoplex technology to improve persistence and functionality of the CAR-T cells.
The candidate is currently in a phase 1/2 study for advanced solid tumors. Data from the ongoing trial showed encouraging antitumor activity in patients and exhibited an overall response rate of 59% and a 95% disease control rate. Its other T cell candidate BNT221 is being studied in patients with refractory metastatic melanoma.
Last month, the biotech paid Autolus Therapeutics $250 million to use the latter’s manufacturing and clinical sites in the U.K. to further develop BNT211.
Cartesian Therapeutics
Cartesian Therapeutics, a clinical-stage biotech company located in the U.S., has developed the first-ever mRNA CAR-T cell therapy for autoimmune diseases. DESCARTES-08 is made up of killer T cells that are designed to hunt down pathogenic plasma cells that secrete auto-antibodies.
At present, it is being evaluated in a phase 2 study for myasthenia gravis, a chronic autoimmune disorder that causes muscle weakness. A phase 2a study showed that the candidate is safe and well-tolerated, and was able to induce durable responses. A phase 2b study has begun enrolling patients.
Cartesian Therapeutics is also investigating DESCARTES-08 in a phase 1 study in patients with systemic lupus erythematosus, an autoimmune condition that causes joint pain, skin rashes and tiredness.
Its pipeline candidates are derived from its RNA Armory platform, which combines precision medicine and cell therapy technology such that patients treated with Cartesian’s CAR-T therapies would not require pre conditioning chemotherapy.
In November, the biopharma merged with U.S.-based Selecta Biosciences, after which the combined company had more than $110 million to support Descartes-08 through to phase 3 in the clinic.
CARGO Therapeutics
Having secured more than $280 million in an initial public offering, American company CARGO Therapeutics has begun a phase 2 trial for its lead CAR-T cell therapy candidate CRG-022. The candidate targets CD22, a B-cell specific antigen that is expressed in more than 8% of diffuse LBCL cases.
As CD22 expression is usually retained after the loss of CD19 antigen expression in patients who become resistant to CD19 CAR-T cell therapy, it is designed to be administered after a patient has been given CD19-targeting CAR-T therapy.
To add to that, Cargo is working to address the loss of costimulatory ligands – molecules expressed by T cells – like CD58. It is doing so by developing CAR-T cells that induce CD2 costimulatory signaling by a tumor antigen regardless of potential CD58 downregulation or loss on tumor cells. This way, the biotech aims to tackle the resistance to immune therapies.
Earlier this year, the company took part in the J.P. Morgan Healthcare Conference, one of the largest healthcare investment symposiums.
Kite Pharma
Known for its autologous CAR-T drug Yescarta to treat LBCL, which was approved by the FDA in 2017, Gilead-owned Kite Pharma is now testing the drug in the clinic to address other forms of lymphoma.
The drug, which contains the active ingredient axicabtagene ciloleucel, is in two phase 3 trials for patients with high-risk follicular lymphoma and high-risk lLBCL, and in another high-risk LBCL phase 2 trial. The drug, however, does come with a boxed warning for side effects such as cytokine release syndrome.
Two months ago, the FDA approved a manufacturing process change that cuts down the manufacturing time for Yescarta. This reduces Kite’s median turnaround time in the U.S. from 16 days to 14 days.
And late last year, it had announced that it would expand its partnership with fellow American biotech Arcellx to advance the latter’s multiple myeloma candidate targeting BCMA, and gain a stronger foothold in the CAR-T space.
Legend Biotech
Among the leaders in CAR-T research, as its drug Carvykti is one of the few FDA-approved CAR-T cell therapies for cancer in the market, Legend Biotech has collaborated with Johnson & Johnson to test cilta-cel (Carvykti) in multiple myeloma drug trials.
Last week, the drug received an FDA recommendation for earlier treatment of patients with relapsed/refractory multiple myeloma. Cilta-cel, which was approved two years ago, is a B-cell maturation antigen (BCMA)-directed autologous CAR-T therapy indicated for the treatment of adults with relapsed or refractory multiple myeloma, who have undergone four or more prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody.
Last month, the European Medicines Agency’s (EMA’s) Committee for Medicinal Products for Human Use (CHMP) recommended expanding the patient population treated with Carvykti to include those patients with relapsed and refractory multiple myeloma, who have received at least one prior therapy.
Previously, the biotech company received $100 million from Swiss drugmaker Novartis to advance its candidate LB2102, with the aid of Novartis’ T-Charge CAR-T cell therapy platform, which helps cut down the culture time outside the body and improve T cell proliferation.
CAR-T cell therapies in the market
The human genome mapping in 2003 laid the foundation for immunotherapy research. Soon enough, scientists in the U.S. began to actualize the idea behind CAR-T therapies, and then, the first-ever CAR-T therapy – Kymriah – was greenlit by the FDA in 2017. The drug, which is developed by Novartis, was cleared to treat patients with refractory/relapsed B-cell precursor acute lymphoblastic leukemia and adult patients with relapsed or refractory diffuse large B-cell lymphoma. Soon after, Yescarta’s approval followed.
Since then, Celgene’s Abecma and Kite’s Tecartus and Carvykti have all hit the market to treat blood cancers. And Bristol Myers Squibb’s Breyanzi, which was first approved in 2021 to treat DLBCL, finally received the go-ahead to treat refractory chronic lymphocytic leukemia and small lymphocytic lymphoma, last week.
As CAR-T engagers are being designed to boost anti-cancer immunity, research in the field continues to progress. And hopefully, concerns regarding cytokine release syndrome can be addressed in the near future.